The physical stability (particle size growth, flocculation rate, sedimentation/creaming behaviors) of a non-aqueous based suspension metered dose inhaler (MDI) formulation is a critical factor that affects the pharmaceutical performance characteristics of the drug product. For a suspension MDI, the key pharmaceutical performance characteristics of the formulation include reproducible dosing, ready dispersibility of the suspended medicament, and minimal particle size change over time.
Water has long been considered to have a negative impact on the physical stability of non-aqueous suspensions. In the literature, the following two aspects are well established:                a) too much water results in altered sedimentation characteristics leading to fast sedimentation and therefore to variability in dose of the suspended active ingredient, and        b) too much water can alter the particle size distribution by contributing to the formation of flocculates and aggregates of the individual drug particles or can cause solubilizing and re-crystallizing of drug particles.        